Bromoform → 2-(Cyclopropylmethoxy)-2-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)acetic acid

HRID 2359224Notes

Reaction equation

HRID 2359224 reaction equation
[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:14]=[CH:13][C:10]([CH:11]=O)=[CH:9][CH:8]=2)=[N:4][N:3]=1.[OH-:15].[K+].C(Br)(Br)Br.[OH-].[K+].[CH:23]1([CH2:26][OH:27])[CH2:25][CH2:24]1.C1([CH2:31][OH:32])CC1>O1CCOCC1>[CH:23]1([CH2:26][O:27][CH:11]([C:10]2[CH:13]=[CH:14][C:7]([C:5]3[O:6][C:2]([CH3:1])=[N:3][N:4]=3)=[CH:8][CH:9]=2)[C:31]([OH:32])=[O:15])[CH2:25][CH2:24]1

Participants

7

Reactant 5

HCID 5558BromoformHCID 14797Potassium HydroxideHCID 75644Cyclopropanemethanol2×HCID 106552074-(5-Methyl-1,3,4-oxadiazol-2-yl)benzaldehydeHCID 86657504KOH cyclopropylmethanol

Product 1

HCID 584320792-(Cyclopropylmethoxy)-2-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)acetic acid

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 4-(5-methyl-1,3,4-oxadiazol-2-yl)benzaldehyde (5.3 g, 27.7 mmol) in cyclopropylmethanol (25 mL) and anhydrous dioxane (25 mL) at 0° C. (bath temperature) was added several drops of a solution of KOH (7.77 g, 138.5 mmol) in cyclopropylmethanol (35 mL). Bromoform (3.1 mL, 35.2 mmol) was added, then the remaining KOH/cyclopropylmethanol solution was added over a period of 20 min. After stirring for 30 min, the reaction mixture was allowed to warm slowly to room temperature overnight then concentrated to dryness. After dissolving in a minimum amount of H2O, the residue was acidified to pH 1 with concentrated HCl. The aqueous mixture was extracted with EtOAc several times with the addition of brine to the aqueous layer during extraction. The combined organics were washed with brine, dried over Na2SO4 and concentrated in vacuo to give 2-(cyclopropylmethoxy)-2-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)acetic acid as a semisolid which was then recyrstallized from Et2O (0.5 g, 7% yield).

Workup

  1. concentrationthen concentrated to dryness
  2. dissolutionAfter dissolving in a minimum amount of H2O
  3. extractionThe aqueous mixture was extracted with EtOAc several times with the addition of brine to the aqueous layer during extraction
  4. washThe combined organics were washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b2fe0d08623c4b588f3f9b47ca57ccc6
Source dataset
uspto-grants-2014_04
Patent number
US08685975B2

Reaction notes

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